There is increasing recognition that prostate cancer and breast cancer demonstrate significant clustering in some families. What is not known, however, is whether this observation is due to coincidence, common environment, or are flection of inherited susceptibility. The purpose of the proposed research is to investigate the genetic epidemiology of breast-prostate cancer in a nested case-control family study within an ongoing cohort study of 544 highly characterized 4- and 5- generation families initially ascertained through a proband with breast cancer at the University of Minnesota between 1944 and 1952 (R01 CA55747, T. Sellers, P.I.). From this larger cohort, the investigators propose to select 50 case families in which at least 4 women have developed breast or ovarian cancer, and two control groups: a) control families in which only the original proband developed breast cancer and b) men who have married into the case families. The occurrence of prostate cancer will be determined among a) brothers, sons, nephews, and grandsons of the case and control probands, and b) the spouses of first- and second- degree female family members in the case families. Data will be collected by telephone interview and mailed questionnaires to assess those environmental and lifestyle exposures that might promote the clustering of breast and prostate cancer within these families for non-genetic reasons. Detailed analyses of family history will be performed to see if there is an excess occurrence of prostate cancer in the case families compared with the two control groups. Analyses of individual family members will be performed to determine if any observed excesses of prostate cancer can be attributed to measure non-genetic risk factors. Complex segregation analysis, incorporating environmental covariates, will be performed to determine whether the familial aggregation of breast and prostate is consistent with a Mendelian pattern of inheritance. This will be performed using the REGTL software program in Statistical Analysis for Genetic Epidemiology (SAGE) and Pedigree Analysis Package (PAP). Finally, blood samples will be collected as a source of genomic DNA for future studies to explore the role of several candidate genes on the susceptibility to these hormone-dependent malignancies.